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Stratifying risk of recurrence in stage II colorectal cancer using deregulated stromal and epithelial microRNAs

Stratifying risk of recurrence in stage II colorectal cancer using deregulated stromal and epithelial microRNAs
Stratifying risk of recurrence in stage II colorectal cancer using deregulated stromal and epithelial microRNAs
MicroRNAs (miRNAs) enable colonic epithelial cells to acquire malignant characteristics and metastatic capabilities. Recently, cancer relevant miRNAs deregulated during disease progression have also been identified in tumor-associated stroma.By combining laser-microdissection (LMD) with high-throughput screening and high-sensitivity quantitation techniques, miRNA expression in colorectal cancer (CRC) specimens and paired normal colonic tissue was independently characterized in stromal and epithelial tissue compartments. Notably, deregulation of the key oncogene miR-21 was identified exclusively as a stromal phenomenon and miR-106a, an epithelial phenomenon in the malignant state.MiRNAs identified in this study successfully distinguished CRC from normal tissue and metastatic from non-metastatic tumor specimens. Furthermore, in a separate cohort of 50 consecutive patients with CRC, stromal miR-21 and miR-556 and epithelial miR-106a expression predicted short disease free survival (DFS) and overall survival (OS) in stage II disease: miR-21 (DFS: HR = 2.68, p = 0.015; OS: HR = 2.47, p = 0.029); miR-556 (DFS: HR = 2.60, p = 0.018); miR-106a (DFS: HR = 2.91, p = 0.008; OS: HR = 2.25, p = 0.049); combined (All High vs. All Low. DFS: HR = 5.83, p = 0.002; OS: HR = 4.13, p = 0.007).These data support the notion that stromal as well as epithelial miRNAs play important roles during disease progression, and that mapping patterns of deregulated gene expression to the appropriate tumor strata may be a valuable aid to therapeutic decision making in CRC.
colorectal cancer, microRNA, stroma, tumor microenvironment
1949-2553
7262-7279
Bullock, Marc D.
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Pickard, Karen
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Mitter, Richard
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Sayan, A. Emre
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Primrose, John N.
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Ivan, Cristina
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Calin, George A.
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Thomas, Gareth J.
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Packham, Graham K.
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Mirnezami, Alex H.
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Bullock, Marc D.
e060d2b2-5e6f-449b-b8ae-f411b5a396c2
Pickard, Karen
e5188669-dff1-49c7-9c6f-8122b0c74bd9
Mitter, Richard
5d4318fc-b6da-4a5b-8a88-5815e9e51b9a
Sayan, A. Emre
5590c6d1-6562-46be-a002-98adc087f1b6
Primrose, John N.
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Ivan, Cristina
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Calin, George A.
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Thomas, Gareth J.
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Packham, Graham K.
fdabe56f-2c58-469c-aadf-38878f233394
Mirnezami, Alex H.
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Bullock, Marc D., Pickard, Karen, Mitter, Richard, Sayan, A. Emre, Primrose, John N., Ivan, Cristina, Calin, George A., Thomas, Gareth J., Packham, Graham K. and Mirnezami, Alex H. (2015) Stratifying risk of recurrence in stage II colorectal cancer using deregulated stromal and epithelial microRNAs. Oncotarget, 6 (9), 7262-7279. (doi:10.18632/oncotarget.3225). (PMID:25446899)

Record type: Article

Abstract

MicroRNAs (miRNAs) enable colonic epithelial cells to acquire malignant characteristics and metastatic capabilities. Recently, cancer relevant miRNAs deregulated during disease progression have also been identified in tumor-associated stroma.By combining laser-microdissection (LMD) with high-throughput screening and high-sensitivity quantitation techniques, miRNA expression in colorectal cancer (CRC) specimens and paired normal colonic tissue was independently characterized in stromal and epithelial tissue compartments. Notably, deregulation of the key oncogene miR-21 was identified exclusively as a stromal phenomenon and miR-106a, an epithelial phenomenon in the malignant state.MiRNAs identified in this study successfully distinguished CRC from normal tissue and metastatic from non-metastatic tumor specimens. Furthermore, in a separate cohort of 50 consecutive patients with CRC, stromal miR-21 and miR-556 and epithelial miR-106a expression predicted short disease free survival (DFS) and overall survival (OS) in stage II disease: miR-21 (DFS: HR = 2.68, p = 0.015; OS: HR = 2.47, p = 0.029); miR-556 (DFS: HR = 2.60, p = 0.018); miR-106a (DFS: HR = 2.91, p = 0.008; OS: HR = 2.25, p = 0.049); combined (All High vs. All Low. DFS: HR = 5.83, p = 0.002; OS: HR = 4.13, p = 0.007).These data support the notion that stromal as well as epithelial miRNAs play important roles during disease progression, and that mapping patterns of deregulated gene expression to the appropriate tumor strata may be a valuable aid to therapeutic decision making in CRC.

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Accepted/In Press date: 27 January 2015
Published date: 7 March 2015
Keywords: colorectal cancer, microRNA, stroma, tumor microenvironment
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 380565
URI: https://eprints.soton.ac.uk/id/eprint/380565
ISSN: 1949-2553
PURE UUID: 421c15a1-6180-4efa-9d88-2bc5bcc68070
ORCID for John N. Primrose: ORCID iD orcid.org/0000-0002-2069-7605
ORCID for Graham K. Packham: ORCID iD orcid.org/0000-0002-9232-5691

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Date deposited: 11 Sep 2015 15:37
Last modified: 15 Aug 2019 00:54

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Contributors

Author: Marc D. Bullock
Author: Karen Pickard
Author: Richard Mitter
Author: A. Emre Sayan
Author: Cristina Ivan
Author: George A. Calin

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